Extensive epidemiological data support the notion that individuals are not equally susceptible to HIV infection and that host genetic variations play critical roles in influencing HIV infection and disease progression. Previous studies have also demonstrated that genetic variation can be unevenly distributed among populations, and the same polymorphism can differently modify HIV transmission and disease progression in different races. In our preliminary studies, we demonstrated that DC-SIGN and DC-SIGNR repeat region polymorphisms affect HIV transmission in U.S. cohorts. Moreover, we identified DC-SIGN repeat region variations in Chinese populations and Chinese individuals with DC-SIGN repeat region variations are significantly more frequent in HIV negative than in HIV positive individuals. Compared with the U.S. cohort, Chinese individuals are significantly more likely to have more DC-SIGN repeat region variations. These results underline the necessity to evaluate other populations, as we proposed in this study. Globally, heterosexual transmission is the most often route for adult HIV infection. Therefore, nearly half of all HIV infected adults are women of child-bearing age. Despite advance in prevention, about 2,000 new pediatric HIV cases occur daily in the world, of which 200 cases occur in India. In addition, the limited information of host genetic polymorphisms from India and the recent alert that the genetic makeup of Indians may favor a fast and easy spread of AIDS prompt us to identify host genetic polymorphisms that influence HIV mother to child transmission (MTCT) and sexual transmission in India. Study subjects consist of 1,500 Indian individuals, including HIV positive and negative adults and children, HIV discordant couples, and HIV positive mothers. Our proposal will focus on the following Specific Aims: 1), To determine if the prevalence of DC-SIGN and DC-SIGNR repeat region and promoter variations in Indian populations are different from the US populations; and 2), To evaluate if DC-SIGN and DC-SIGNR repeat region and promoter variations influence HIV MTCT and sexual transmission in Indian populations. These studies will provide insights in identifying new host genetic variations that influence HIV disease in India populations, developing new therapeutic targets and strategies to control the alarming AIDS epidemic in India. [unreadable] [unreadable] [unreadable]